Chromosomal Aberrations in Squamous Cell Carcinoma and Solar Keratoses Revealed by Comparative Genomic Hybridization

Ashton, Kevin J.; Weinstein, Stephen R.; Maguire, David; Griffiths, Lyn R.

doi:10.1001/archderm.139.7.876

Cited by 72 publications

(61 citation statements)

References 45 publications

(68 reference statements)

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“…In one study (Quinn et al, 1994) of 47 tumors frequent LOH of markers was observed on 9p (41%), 13q (46%), 17p (33%), 17q (33%), and 3p (23%). More recently, comparative genomic hybridization (CGH) has been used to identify genome-wide chromosomal imbalances within SCC (Popp et al, 2002;Ashton et al, 2003;Clausen et al, 2006). Despite considerable variation, the combined data from these three studies suggest a characteristic pattern of genetic aberrations within SCC.…”

Section: Resultsmentioning

confidence: 99%

Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis

Purdie

Lambert

Teh

et al. 2007

Genes Chromosomes & Cancer

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Cutaneous squamous cell carcinomas (SCC) are the second most commonly diagnosed cancers in fair-skinned people; yet the genetic mechanisms involved in SCC tumorigenesis remain poorly understood. We have used single nucleotide polymorphism (SNP) microarray analysis to examine genome-wide allelic imbalance in 16 primary and 2 lymph node metastatic SCC using paired nontumour samples to counteract normal copy number variation. The most common genetic change was loss of heterozygosity (LOH) on 9p, observed in 13 of 16 primary SCC. Other recurrent events included LOH on 3p (9 tumors), 2q, 8p, and 13 (each in 8 SCC) and allelic gain on 3q and 8q (each in 6 tumors). Copy number-neutral LOH was observed in a proportion of samples, implying that somatic recombination had led to acquired uniparental disomy, an event not previously demonstrated in SCC. As well as recurrent patterns of gross chromosomal changes, SNP microarray analysis revealed, in 2 primary SCC, a homozygous microdeletion on 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus, an emerging frequent target of homozygous deletion in lung cancer and neuroblastoma. A third sample was heterozygously deleted within this locus and PTPRD expression was aberrant. Two of the 3 primary SCC with PTPRD deletion had demonstrated metastatic potential. Our data identify PTPRD as a candidate tumor suppressor gene in cutaneous SCC with a possible association with metastasis.

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Section: Resultsmentioning

confidence: 99%

Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis

Purdie

Lambert

Teh

et al. 2007

Genes Chromosomes & Cancer

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“…Despite the high morbidity rate and the increasing number of metastasis, the genetic knowledge of skin SCCs is still poor (reviewed in Ashton et al, 2003). Furthermore, the data presented to date still lack identification of specific aberrations present in the majority of tumors, thus hampering efforts to identify common pathways for skin cancer development.…”

Section: Discussionmentioning

confidence: 99%

“…One CGH study was previously applied on KAs, demonstrating a high frequency of tumors without genetic alterations (about 65%) and only low frequency of recurrent alterations, for example, gain of 8q and loss of 3p, 9p or 19p in 20% of the tumors (Clausen et al, 2002). As these changes were, however, also among those characteristically seen in SCCs (Jin et al, 1999;Popp et al, 2000Popp et al, , 2002Jin et al, 2002;Ashton et al, 2003), KAs and SCCs likely share a common developmental history and it is reasonable to propose that increasing our knowledge on the genetics of KAs is an important step in elucidating the crucial changes involved in the initiation of skin cancer.…”

Section: Introductionmentioning

confidence: 99%

Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation

Burnworth¹,

Popp²,

Stark³

et al. 2006

Oncogene

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Non-melanoma skin cancers, in particular keratoacanthomas (KAs) and squamous cell carcinomas (SCCs), have become highly frequent tumor types especially in immunesuppressed transplant patients. Nevertheless, little is known about essential genetic changes. As a paradigm of 'early' changes, that is, changes still compatible with tumor regression, we studied KAs by comparative genomic hybridization and show that gain of chromosome 11q is not only one of the most frequent aberration (8/18), but in four tumors also the only aberration. Furthermore, 11q gain correlated with amplification of the cyclin D1 locus (10/14), as determined by fluorescence in situ hybridization, and overexpression of cyclin D1 protein (25/31), as detected by immunohistochemistry. For unraveling the functional consequence, we overexpressed cyclin D1 in HaCaT skin keratinocytes. These cells only gained little growth advantage in conventional and in organotypic cocultures. However, although the control vector-transfected cells formed a well-stratified and orderly differentiated epidermis-like epithelium, they showed deregulation of tissue architecture with an altered localization of proliferation and impaired differentiation. The most severe phenotype was seen in a clone that additionally upregulated cdk4 and p21. These cells lacked terminal differentiation, exhibited a more autonomous growth in vitro and in vivo and even formed tumors in two injection sites with a growth pattern resembling that of human KAs. Thus, our results identify 11q13 gain/cyclin D1 overexpression as an important step in KA formation and point to a function that exceeds its known role in proliferation by disrupting tissue organization and thereby allowing abnormal growth.

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“…Inactivation of chromosome 18q is identified not only in colorectal carcinoma, 33 but also in pancreatic, 34 gastric, 35 small intestinal, 36 appendiceal, 37 breast, 38 prostatic 39 and squamous cell carcinomas. 40,41 DPC4 (Smad4) gene inactivation is present in pancreatic, 34 small intestinal 36 and appendiceal carcinomas, 37 but is uncommon in other malignancies. 42,43 Data from the present study and the previous studies show that chromosome 18q loss is infrequent in pancreatic endocrine tumors 44 but common in midgut carcinoid tumors 32 and goblet cell carcinoid tumors of appendix.…”

Section: Discussionmentioning

confidence: 99%

“…45 Allelic loss at 18q12.3-q23 was reportedly common in squamous cell carcinoma but not in solar keratoses. 40 Also, loss of chromosome18p may be associated with adverse clinical outcome in patients with high-risk breast cancer. 46 Other putative tumor suppressor genes localized immediately telomeric to DCC and DPC4 at microsatellite locus 18q21.3 are serpins (Serine Proteinase Inhibitors) some of which (maspin) reportedly can suppress tumor growth and spread in breast carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors

et al. 2005

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Carcinoid tumors and pancreatic endocrine tumors are uncommon neuroendocrine neoplasms, and their genetic alterations are not well characterized. These tumors have site-specific differences in neuroendocrine characteristics, clinical course and genetic alterations. We compared clinicopathological features and loss of heterozygosity of chromosomes 11q, 16q and 18, and BRAF gene mutations in 47 patients with neuroendocrine tumors including 16 with pancreatic endocrine tumors, 15 with nonileal carcinoid tumors and 16 with ileal carcinoid tumors. Patients with carcinoid tumors had more frequent history of alcohol consumption compared to patients with pancreatic endocrine tumors (P ¼ 0.02), and patients with ileal carcinoid tumors more frequently had liver metastasis compared to patients with nonileal carcinoid tumors and pancreatic endocrine tumors (P ¼ 0.02). Allelic loss of chromosome 11q was present in 21% of tumors, chromosome 16q in 13%, and chromosome 18 in 30%. These alterations differed with the anatomical subsite of tumor: allelic loss of chromosome 18 was present in 69% of ileal carcinoid tumors, 13% of nonileal carcinoid tumors and 6% of pancreatic endocrine tumors (P ¼ 0.001). In contrast to pancreatic endocrine tumors and nonileal carcinoid tumors, all 11 ileal tumors with loss of chromosome 18 had complete loss of both chromosomal arms. No BRAF mutations were identified. Complete allelic loss of chromosome 18 was associated with smaller tumor size (P ¼ 0.02). Our study indicates that genetic alterations vary by tumor subsite and clinicopathologic features, and ileal carcinoid tumors have distinctive clinicopathologic and genetic profiles.

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Chromosomal Aberrations in Squamous Cell Carcinoma and Solar Keratoses Revealed by Comparative Genomic Hybridization

Cited by 72 publications

References 45 publications

Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis

Allelic imbalances and microdeletions affecting the PTPRD gene in cutaneous squamous cell carcinomas detected using single nucleotide polymorphism microarray analysis

Gain of 11q/cyclin D1 overexpression is an essential early step in skin cancer development and causes abnormal tissue organization and differentiation

Comparison of genetic alterations in neuroendocrine tumors: frequent loss of chromosome 18 in ileal carcinoid tumors

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